Definition

Anaphylaxis is any acute onset of hypotension, bronchospasm or upper airway obstruction where anaphylaxis is considered possible. Even if typical skin features are not present OR any acute onset illness with typical skin features (urticarial rash or erythema/flushing and/or angioedema) PLUS involvement of respiratory and/or cardiovascular and/or persistent severe gastrointestinal symptoms.

Epidemiology

Anaphylaxis is generally under-reported and many unexplained deaths could be anaphylaxis. Statistically, the facts are difficult to collate due to various factors such as different hospital codes and the cause of death may not be specifically attributed to anaphylaxis, but natural causes.

Source: Australasian Society of Clinical Immunology and Allergy

Pathophysiology

Anaphylaxis the most severe form of an allergic reaction. Immediate allergic reactions are due to an interaction between Immunoglobulin-E (IgE) antibodies and an antigen (allergen) with a resulting release of chemicals from cells such as basophils and mast cells.

Review of a normal immune response (antigen/antibody reaction):

• Antigen:
  • Substances (usually a protein) that enter your body and induce the formation of antibodies. These may sometimes referred to as allergens. A substance that is an allergen for one person may not be for another.
    
• Antibody:
  • Neutralises antigens and removes them from the body.
• Immunoglobulin E (IgE):
  • Accounts for less than 1% of antibodies in normal serum. Responsible for immediate hypersensitivity reactions
• Basophil:
  • A white blood cell that promotes inflammation
• Mast cell:
  • Distributed amongst connective tissues (skin, lungs, GI tract which is where allergens are mostly likely to enter the body) . Filled with vasoactive amines (histamine, serotonin, leukotrienes).
    Mast cells release amines as part of the inflammatory response. They have a role in defending the body against parasites and they have receptors for IgE antibody on their surface.
    This release is stimulated by antigens binding to IgE, injury (i.e. trauma) or chemical agents (e.g. toxins, or in some people, physical stresses such as exercise).  
    

Antigens may enter the body by:

• Injection
• Ingestion
  
• Inhalation
  
• Absorption

Antigens will enter the system and trigger an immune response which leads to the production of antibodies (or immunoglobulins) which are designed to fight the invading antigens by binding to them and causing degranulation of the cell. This degranulation will cause a release of the chemicals that will fight the invading cells, such as histamine.

This normal antigen– antibody reaction is what protects the body from disease by activating the immune response. The immune responses are normally protective, however they can become oversensitive and become directed toward harmless antigens to which we often are exposed; this response is known as an allergic response.

Mild to moderate allergic reactions

These reactions do not involve the circulatory or respiratory system. They usually occur minutes to 2 hours of exposure to an allergen.

Mild to moderate symptoms:

• Hives or welts
• Tingling mouth
• Angioedema (swelling of lips, face, eyes)
• Abdominal pain (this is a sign of anaphylaxis to medications and insect stings and bites)
• Vomiting (this is a sign of anaphylaxis to medications and insect stings and bites)
  

Treatment is typically with non-sedating antihistamines, which compete at the receptor sites with histamine. By doing so, this prevents histamine from performing its physiological actions. An antihistamine can help with the skin symptoms of an allergic reaction (like hives or swelling). They will not treat anaphylaxis.

Anaphylaxis

Anaphylaxis is usually rapidly progressing and is an acute hypersensitivity reaction that can affect multiple organ systems. It is a severe life threatening event which may impact one or more of the cardiovascular or respiratory systems.

Anaphylaxis is caused by the widespread release of inflammatory mediators which results in a systemic increase in capillary permeability, smooth muscle contractility and peripheral vasodilation. Allergic sensitisation occurs when an antigen enters the body and activates the immune system response, leading to the production of IgE antibodies directed against that antigen. These antibodies then remain inactive on the cells until another exposure to the antigen and are referred to as antigen specific immunoglobulins.

When the antigen enters the body again, it binds to the IgE antibodies on mast cells and basophils. This interaction  causes degranulation of the cell and the release of chemical mediators to fight the allergen. 

These chemical mediators include:

• histamines
• leukotrienes
• heparin
  
• kinins
  
• prostaglandins
  
• thromboxanes

The effects of these chemical mediators include:

• An increase in the permeability of vessels
• Causes dilation of capillaries and venules (causing flushing & angioedema)
• Plasma leaks into interstitial space (decreases intravascular fluid volume and causes swelling)
• Vasodilation further decreases cardiac preload, decreasing stroke volume and cardiac output (hypotension)
• Contraction of smooth muscle in the GI tract and bronchial tree (associated with increases in gastric, nasal and lacrimal secretions and bronchospasm)

Because the body sees the allergen as dangerous, it tries to protect the body from this perceived invader, just as it would a harmful parasite. Antihistamines do not prevent or treat anaphylaxis as they don’t work against all the mediators and they don’t work immediately. Adrenaline reverses most of the effects listed above and it works within minutes so it is the treatment of choice for anaphylaxis.

Causes

Common causes of anaphylaxis are:

• Medications (e.g. antibiotics such as penicillin)
  
• Food (e.g., peanuts, tree nuts, cow’s milk, egg, wheat, fish, shellfish, sesame, soy (note; any food can induce anaphylaxis))
• Envenomation (bee, wasp and ant stings, tick bites)
• Latex
• In some people, physical stresses (e.g. exercise (with or without prior food ingestion) or immersion in cold water) can lead to an anaphylaxis like reaction.
• Some people may have idiopathic anaphylaxis (no cause identified)
  

Signs and Symptoms

Symptom onset depends on the route of exposure:

• Injection: Average onset 5 to 30 minutes
• Ingestion: Within minutes, and may take up to 2 hours

Anaphylaxis is characterised by any one or more of the following (typically rapidly developing) symptoms:

• Difficult/noisy breathing.
• Swelling of tongue
• Swelling/tightness in throat
• Difficulty talking and/or hoarse voice
• Wheeze or persistent cough. 
• Persistent dizziness and/or collapse
• Change of consciousness
• Hypotension
• Pale and floppy (young children)
  

Complications

Anaphylactic Shock

• Inadequate tissue perfusion due to, widespread vasodilation and increased vascular permeability leading to reduced cardiac output and cardiac failure secondary to an allergic response